Azines and azoles. CXX. Synthesis of acyclic analogs of N 1-ribosides of barbituric acid and its 5-ylidene derivatives

Article abstract of DOI:10.1023/B:RUGC.0000025513.88248.94

The reaction of 2,4,6-tris(trimethylsiloxy)pyrimidine with 2-oxabutane-1,4-diyl diacetate in methylene chloride in methylene chloride in the presence of SnCl₄ proceeds regioselectively to form 1-[(2-acetoxyethoxy)methyl]barbituric acid. The latter is readily deacetylated to a free acyclic analog of N-ribosides of barbituric acid. 1-[(2-Acetoxy- and 2-hydroxyethoxy)methyl]barbituric acids easily react with aromatic and heterocyclic aldehydes in water and organic solvents, forming 5-ylidenebarbituric acids. The structure of the products was proved by ¹H NMR and UV spectroscopy. Certain of the products exhibit a moderate antimicrobial and antiviral activity.

Full text of DOI:10.1023/B:RUGC.0000025513.88248.94

Russian Journal of General Chemistry, Vol. 74, No. 2, 2004, pp. 261 265. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 2, 2004,
pp. 293 298.
Original Russian Text Copyright
2004 by Studentsov, Kokhanovskii, Ganina, Nikolaeva, Fedorova, Moskvin, Ivin.
1
Azines and Azoles. CXX. Synthesis of Acyclic Analogs
1
of N -Ribosides of Barbituric Acid and Its 5-ylidene Derivatives
E. P. Studentsov, A. N. Kokhanovskii, M. B. Ganina, N. I. Nikolaeva,
E. V. Fedorova, A. V. Moskvin, and B. A. Ivin
St. Petersburg State Institute of Technology, St. Petersburg, Russia
St. Petersburg State Chemical and Pharmaceutical Academy, St. Petersburg, Russia
Received March 21, 2003
Abstract The reaction of 2,4,6-tris(trimethylsiloxy)pyrimidine with 2-oxabutane-1,4-diyl diacetate in
methylene chloride in methylene chloride in the presence of SnCl4 proceeds regioselectively to form
1
-[(2-acetoxyethoxy)methyl]barbituric acid. The latter is readily deacetylated to a free acyclic analog of
N-ribosides of barbituric acid. 1-[(2-Acetoxy- and 2-hydroxyethoxy)methyl]barbituric acids easily react with
aromatic and heterocyclic aldehydes in water and organic solvents, forming 5-ylidenebarbituric acids. The
1
structure of the products was proved by H NMR and UV spectroscopy. Certain of the products exhibit a
moderate antimicrobial and antiviral activity.
Derivatives of 5-arylmethylenebarbituric acids
present interest as nontoxic influenza medicines. Their
activity is increased by introduction of a ribosyl
substituent in the pyrimidine ring to form a structure
similar to natural nucleosides [2, 3], on account of a
strongly enhanced solubility of the resulting com-
pounds, enhanced penetrability through cell
membranes, and ability to convert in vivo into the
corresponding nucleotides. Moreover, N-(5 -phospho-
Chromatographic and spectral study showed that
2,4,6-tris(trimethylsiloxy)pyrimidine (II) readily reacts
with 2-oxabutane-1,4-diyldiacetate (III) at a 1:1.2
molar ratio in methylene chloride in the presence of
0.6 mol of SnCl at 18 25 C within 22 24 h, forming
4
a single product, 1-[(2-acetoxyethoxy)methyl]barbituric
acid (IV) (yield ~90%). The catalyst was then re-
moved by adding dimethyl sulfoxide as a strong com-
plex [SnCl4 2DMSO] insoluble in methylene chlo-
ride. Acetate IV was deacetylated in mild conditions
by treatment with 3% methanolic HCl or 20% aque-
ous-alcoholic dimethylamine to obtain 1-[(2-hydroxy-
ethoxy)methyl]barbituric acid (V) in high yield. The
process is well reproducible and easily scaled.
-D-ribofuranosyl)barbituric acid is known as a strong
inhibitor of orothidyl decarboxylase, a key enzyme in
the biosynthesis of pyrimidine nucleosides [4].
Noteworthy is also the fact that acyclic analogs of
uridine and thymidine are efficient antiviral agents; in
particular,
1-[(2-hydroxyethoxy)methyl]-6-(phenyl-
1
The H NMR spectrum of a solution of compound
thio)thymine (HEPT) specifically inhibits HIV-1
replication [5, 6]. Proceeding with search for new bio-
logically active compounds among polyhydroxypyr-
imidine derivatives, we have synthesized acyclic
analogs of N-ribosides of barbituric acid and its
IV in CDCl contains acetyl ( 2.09 ppm, 3H) and
C H ( 3.67 ppm) singlets and C H and C H tri-
plets ( 3.84 and 4.21 ppm). The spectrum of a solu-
tion of compound V in CDCl shows a multiplet of
the N-alkoxymethyl group ( 3.48 3.71 ppm) and a
broadened OH singlet ( 4.41 ppm) and lacks acetyl
signals. Furthermore, the spectra both contain py-
rimidine N H ( 9.08 and 11.37 ppm) and C H (5.39
3
1
3
4
2
2
2
3
5-ylidene derivatives.
Earlier we found [7, 8] that the ribosylation of
barbituric acid with 1,2,3,5-tetra-O-acetyl- -D-ribo-
3
5
2
furanose by the silyl procedure gives rise to a mixture
and 5.20 ppm) signals. In the electronic spectra of
acyclic ribosides IV and V in 0.1 M NaOH, there are
1
1
3
of N -mono- and N ,N -bis(2,3,5-tri-O-acetyl- -D-
ribofuranosyl)barbituric acids; the latter are readily
deacetylated to form N-ribosides of barbituric acids
which react with benzaldehydes, yielding ribosides of
absorption maxima at 260 262 nm (log
4). The
spectra of 0.1 M HCl solutions show in this range a
shoulder with a low molar absorptivity, which is
1
5-arylmethylenebarbituric acids.
characteristic of N -alkyl derivatives of barbituric
acid [9].
1
For communication CXIX, see [1].
N-Acycloribosides IV and V, like other ribosides
1
070-3632/04/7402-0261 2004 MAIK Nauka/Interperiodica

262
STUDENTSOV et al.
OSiMe3
O
(
Me Si) NH, (NH ) SO , 130 140 C
N
HN
3
2
4 2
4
Me SiO
N
OSiMe3
O
N
H
O
3
I
II
O
OAc
(
1) AcO
CH Cl , SnCl ;
(III),
2
2
4
(
2) DMSO;
(
3) MeOH
O
O
+
H or OH
HN
HN3
2
4
5
6
1
N
1
O
N
O
O
O
3
O
O
HO 4
AcO
2
V
IV
PhCHO
RCHO
VIIa VIIm
VI
R = 4-Et NC H (a), 4-Me NC H (b), 4-HOC H (c), 3-MeO-4-HOC H (d), 4-MeOC H (e), 3,4-(MeO) C H (f),
2
6
4
2
6
4
6
4
6
3
6
4
2 6 3
4
-MeC H (g), Ph (h), 4-ClC H (i), 3-chloro-5-ethoxyphenyl-4-[2-(2-methoxyphenoxy)ethoxy]- (j), 5-(4-chlorophenyl)-
6 4 6 4
2
-furyl (k), indol-3-yl (l), 2-methylindol-3-yl (m).
of barbituric acid [7], enter Knoevenagel condensation
with aromatic and heterocyclic aldehydes at equimolar
reagent ratios in water, alcohol, or chloroform in the
presence or in the absence of acids. The best results
were obtained in the reactions of compound V with
aldehydes in water or aqueous alcohol with or without
acetic acid added, depending on the reactivity of the
aldehyde. With acetate IV, chloroform is used as
solvent. The reactions of compounds IV and V with
aldehydes are complete within 2 3 h at 50 80 C,
forming characteristically colored products which
crystallize chromatographically pure directly from the
reaction mixture in 80 90% yield. 5-Arylmethylene
derivatives VII of riboside V are hydrolytically stable
and give hydration products by the exocyclic C=C
bond, which usually easily decompose into the parent
aldehydes and barbituric acids.
yield 5-(2,4-dioxo-1,3,4,5-tetrahydro-2H-chromeno-
[2,3-d]pyrimidin-5-yl)barbituric acids [10 12] and
5,5 -(2-oxo-2,3-dihydro-1H-indol-3,3-diyl)dibarbituric
acids [13], respectively.
The purity of VI and VII was established by TLC,
their elemental composition, by elemental analysis,
1
and structure, by UV and H NMR spectroscopy
1
(
Tables 1 and 2). The H NMR spectra of compounds
1
3
4
VI and VII preserve C H, C H, and C H signals at
.52 5.28 ppm, observed in the spectra of the start-
ing compounds IV and V, lack C H signals, and
3
5
acquire a singlet of the methine proton ( 8.20
8
.82 ppm) and signals of the aromatic or heterocyclic
1
substituents ( 6.78 8.82 ppm). A feature of the H
NMR spectra of compounds VI and VII is doubling
3
of the N H signal at 11.16 11.70 ppm, assignable
to the fact that these compounds exist as two geometric
isomers with different orientations of the aryl (heteryl)
substituent with respect to the C=C bond. The possibi-
lity of geometric isomerism in 5-ylidene derivatives of
barbituric acid arises when one or two different
Thus we synthesized 1-[(2-acetoxyethoxy)methyl]-
-benzylidenebarbituric acid (VI) and 1-[(2-hydroxy-
5
ethoxy)methyl]-5-(arylmethylene)barbituric acids
VIIa VIIm. It should be noted that 1-[(2-hydroxy-
ethoxy)methyl]barbituric acid (V), by TLC data, fails
to react with salicyl aldehyde and 2-hydroxy-3-
methoxybenzaldehyde on prolonged heating in
aqueous alcohol, dioxane, and acetic acid, as well as
with isatin on heating in dilute hydrochloric acid,
unlike barbituric acid and its N-methyl derivatives,
whose reactions with salicyl aldehydes and isatins
1
3
substituents are attached to N or/and N . It can also
be noted that in the spectra of compounds VIIl and
VIIm, this signal is much broadened, and near
12.67 ppm we observe an indole NH signal.
The UV spectra of methanol solutions of com-
pounds VI and VII contain two absorption maxima.
One of them, that is lacking in the spectra of the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 2 2004

AZINES AND AZOLES. CXX.
263
Table 1. Yields, melting points, TLC data, and elemental analyses of 1-[(2-hydroxyethoxy)methyl]-5-[aryl(hetaryl)-
methylene]barbituric acids VIIa VIIm
Found, %b
H
Calculated, %
Comp.
no.
R
Yield, % mp, C Rfa
Formula
C
N
C
H
N
VIIa
VIIb
VIIc
VIId
VIIe
VIIf
VIIg
VIIh
VIIi
VIIj
4-Et NC H
97
94
97
91
92
97
96
80
63
81
191 192 0.50 59.82 6.41 11.62 C H N O
59.78 6.45 11.64
57.63 5.73 12.58
54.92 4.59 9.17
53.55 4.83 8.35
56.21 5.05 8.77
54.83 5.25 8.03
59.23 5.27 9.18
57.89 4.89 9.67
2
6
4
18 23
3
5
5
6
7
6
7
5
5
4-Me NC H
197 198 0.59 57.65 5.76 12.61 C H N O
2
6
4
16 19 3
4-HOC H
223 224 0.27 54.89 4.62 9.15 C H N O
14 14 2
6
4
3-MeO-4-HOC H
204 205 0.44 53.57 4.79 8.33 C H N O
6
3
15 16 2
4-MeOC H
171 172 0.68 56.24 5.04 8.74 C H N O
15 16 2
6
4
3,4-(OMe) C H
178 179 0.29 54.85 5.19 7.99 C H N O
2
6
3
16 18 2
4-MeC H
186 187 0.43 59.19 5.31 9.21 C H N O
15 16 2
6
4
Ph
117 118 0.66 57.92 4.87 9.65 C H N O
14 14 2
4-ClC H
184 185 0.28 51.78 4.04 8.63 C H ClN O 51.80 4.05 8.59
6
4
14 13 2 5
3-Chloro-5-ethoxy-4-
146 147 0.27 56.13 5.09 5.23 C H ClN O 56.10 5.12 5.27
25 27 2 9
[
2-(2-methoxyphen-
oxy)ethoxy]phenyl
5-(4-Chlorophenyl)-2-
furyl
VIIk
VIIl
91
211 212 0.63 55.32 3.88 7.17 C H ClN O 55.35 3.90 7.20
18 15 2 6
Indol-3-yl
97
74
238 239 0.20 58.36 4.59 12.76 C H N O
58.38 4.57 12.73
59.51 5.04 12.20
1
6
15
3
5
5
VIIm 2-Methylindol-3-yl
237 238 0.21 59.47 4.99 12.24 C H N O
17 17 3
a
b
Eluent chloroform methanol, 6:1; for compound VIIj, eluent chloroform methanol, 4:1. For compounds VIIi VIIl, respectively,
found Cl, %: 10.92, 6.62, 9.07; calculated Cl, %: 10.88, 6.59, 9.03.
starting compounds IV and V, is at 325 460 nm and
2,4,6-Tris(trimethylsiloxy)pyrimidine (II).
A
*
probably belongs to the
transition in the
mixture of 12.8 g of anhydrous barbituric acid (I),
74 ml of hexamethyldisilazane, and 0.25 g of
ammonium sulfate was stirred for 2 3 h until the acid
dissolved completely. Excess hexamethyldisilazane
was removed in a vacuum ( 20 mm) dry argon, after
which siloxypyrimidine II was distilled, yield 30.7 g
(92%), bp 144 145 C (13 mm). The product crystal-
lized when handled in moisture-proof conditions.
extended conjugation system formed by the pyrimi-
dine and arylmethylene fragments. The other ab-
sorption maximum, at 250 275 nm ( 6250
1
8
700 l mol cm ) belongs to the
transition of
the ionized pyrimidine ring. The intensity of this band
decreases as the solution is acidified.
According to data obtained at the Chair of Micro-
biology, Virology, and Immunology, Pavlov St.
Petersburg State Medical Uiversity, compounds VIIa,
VIIc, VIIe, VIIj, and VIIk are moderately active
against mycobacteria (Mycobacterium avium), and
VIIe and VIIm, against viruses (herpes simplex). The
synthesized compounds have exhibited no activity
against Candida and Aspergillius fungi.
1-[(2-Acetoxyethoxy)methyl]barbituric acid (IV).
A solution of 28.8 g of compound III in 30 ml of
methylene chloride was added dropwise with stirring
to a moisture-proof solution of 47 g of siloxypyrim-
idine II in 50 ml of anhydrous methylene chloride.
The mixture was cooled with ice water, and a solution
of 21.3 g of SnCl in 20 ml of methylene chloride was
4
added. After 2-h standing at 18 25 C, a transparent
solution formed, which was left to stand for 12 15 h,
cooled, and treated with 15.4 ml of anhydrous DMSO
(added dropwise). The mixture was left to stand for
1 h at 0 C, the complex SnCl 2Me SO precipitated
EXPERIMENTAL
1
The H NMR spectra of CDCl and DMSO-d
3
6
solutions were recorded on a Bruker AM 200 spec-
trometer. The electronic absorption spectra were
obtained on an SF-26 spectrophotometer in quartz
cells, thickness 1 cm; the concentrations of the solu-
tions were 10 4 10 M. Purity and reaction control
was performed by TCL on Sorbfil plates (UV
detection).
4
2
and was filtered off and washed with methylene
chloride. The filtrate was diluted with 45 ml of an-
hydrous methanol, heated to 40 C within 15 min, and
dried in a vacuum. Methylene chloride, 100 ml, was
added to the solid residue, and the mixture was heated
to boiling and then left to stand for 12 15 h at 4 5 C.
5
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 2 2004

264
STUDENTSOV et al.
1
Table 2. UV and H NMR spectra of 1-[(2-hydroxyethoxy)methyl]-5-[aryl(hetaryl)methylene]barbituric acids VIIa VIIm
1H NMR spectrum (DMSO-d6), , ppm
Comp.
no.
UV spectrum,
max, nm (log )
a
C H , C1 H, C5=CH,
3
3
N H,
2
R
4
C H , m
s
s
two s
2
VIIa
VIIb
250 (3.92), 470 (4.20)
250 (3.94), 460 (4.19)
3.52
3.52
5.26
5.28
8.20
8.39
11.50, 11.70 2.51 s [10H, N(C H ) ], 6.78 m, 8.39 m (4H,
2 5 2
Harom
)
11.19, 11.25 3.15 s [6H, N(CH ) ], 6.78 8.22 m (4H
3
2
Harom
)
VIIc
VIId
262, 385, 460
232 (3.90), 260 (3.96),
3.54
3.52
5.26
5.28
8.30
8.50
11.42, 11.46 6.78 d, 8.3 m (4H, Harom), 10.74 s (1H, OH)
11.40, 11.46 3.85 s (3H, OCH ), 6.89 d, 7.8 m, 8.3 s (3H,
3
4
05 (3.96), 480 (3.98)
Harom), 10.41 s (1H, OH)
VIIe
VIIf
VIIg
VIIh
VIIi
VIIj
245 (3.80), 390 (4.00)
265, 400
265, 430
264 (3.87), 327 (3.83)
223, 262
225, 265
3.56
3.52
3.54
3.54
3.54
3.52
5.30
5.28
5.26
5.28
5.26
5.28
8.35
8.33
8.35
8.40
8.35
8.26
11.35, 11.48 3.9 s (3H, OCH ), 7.04 8.35 m (4H, Harom)
3
11.45, 11.60 7.11 d, 7.87 m, 8.33 m (3H, Harom
)
11.40, 11.46 2.44 s (3H, CH ), 7.3 d, 8.09 m (4H, Harom)
3
11.50, 11.60 7.5 8.07 m (5H, Harom
11.37, 11.42 6.82 8.3 m (4H, Harom
)
)
11.55, 11.65 1.37 t (3H, CH ), 3.72 s (3H, OCH ), 4.24 m
3 3
(
(
6H, CH , OCH CH O), 6.89 s (4H,), 7.94 m
2
2
2
2H, Harom
)
VIIk
VIIl
270, 430
275, 420
3.54
3.54
5.26
5.28
8.61
8.82
11.10, 11.15 7.52 8.2 m (6H, Harom, Hfuran)
11.39 br
7.28 7.85 m, 9.55 (5H, Hindole), 12.76 br.s
1H, NH)
2.58 s (3H, CH ), 7.22 m (4H, Hindole),
(
VIIm
265, 435
3.54
5.28
8.57
11.15 br
3
1
2.58 br.s (1H, NH)
a
Compounds VIIc, VIIf, VIIg, and VIIi VIIm do not completely dissolve in methanol even on prolonged heating; therefore, we do
not give their molar absorptivities.
The precipitate was filtered off, washed with ether,
and dried to obtain 30.4 g (91%) of compound IV as
colorless crystals, mp 112 113 C. The product is
chromatographically pure: Rf 0.56 (chloroform
methanol, 6:1). UV spectrum (0.1 N NaOH), , nm
spectrum (H O), , nm ( ):
spectrum (0.1 N HCl), , nm ( ):
2
max
1
NMR spectrum (DMSO-d ), , ppm: 3.56 m (6H,
6
1
3
4
C H , C H , C H ), 5.15 s (2H, C H ), 11.33 br.s
(1H, N H). Found, %: C 41.60; H 5.03; N 13.54.
C H N O . Calculated, %: C 41.59; H 4.99; N 13.86.
2
2
2
3
(
(
):
262 (12550),
236 (3507). UV spectrum
max
min
7
10
2
5
1
0.1 N HCl),
, nm ( ): 250 255 sh (3904). H
max
b. Compound IV, 2 g, was dissolved in 15 ml of
NMR spectrum (CDCl ), , ppm: 2.08 s (3H, H CCO),
3
3
3
4
methanol with heating. After cooling to 18 25 C,
dimethylamine (5.8 ml of a 5.5 M solution) was
added, and the mixture was left to stand at that
temperature for 12 15 h. The solvent was removed in
a vacuum, the residue was dissolved in methanol, the
3
.69 s (2H, C H ), 3.83 m (2H, C H ), 4.20 m (2H,
2 2
1
3
C H ), 5.35 s (2H, C H ), 8.98 br.s (1H, N H). Found,
2
5
2
%
%
: C 44.30; H 4.91; N 11.78. C H N O . Calculated,
: C 44.27; H 4.95; N 11.47.
9
12
2
6
solution was treated with KU-2 (H ) ion-exchange
1-[(2-Hydroxyethoxy)methyl]barbituric acid (V).
resin, and the resin was filtered off. The filtrate was
reduced by half in a vacuum, diluted with 40 ml of
ether, and left to stand to crystallize compound V.
Yield 1.42 g (86%). The physicochemical and spec-
tral characteristics of the product were identical to
those of the sample obtained by procedure a.
a. A mixture of 10.25 g of compound IV and 130 ml
of 3% methanolic HCl was stirred for 30 min at 40
5
0 C and left to stand for 12 15 h at room tempera-
ture, after which is was reduced by half in a vacuum
and cooled to 0 C. The precipitate that formed was
filtered off, washed with 40 ml of methanol ether,
1
:1, and dried to obtain 7.51 g (88%) of compound V
1-[(2-Acetoxyethoxy)methyl]-5-benzylidene-
barbituric acid (VI). A solution of 1.02 g of benzal-
dehyde in 5 ml of chloroform was added with stirring
to a solution of 2.44 g of compound IV in 15 ml of
as colorless crystals, mp 147 148 C, R 0.4 (chloro-
form methanol, 6:1). UV spectrum (0.1 N NaOH),
f
,
nm ( ):
261 (8782),
240 (3687). UV
max
min
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 2 2004

AZINES AND AZOLES. CXX.
chloroform. The mixture was acidified with 0.1 M
265
REFERENCES
HCl to pH 1 1.5 and heated for 30 min at 40 50 C.
The solvent was removed, and the residue was recrys-
tallized from hexane to obtain 2.45 g (74%) of com-
pound VI as light yellow crystals, mp 96 97 C; Rf
1. Fedorova, E.V., Meshcheryakov, M.P., Ganina, M.B.,
Moskvin, A.V., and Ivin, B.A., Zh. Obshch. Khim.,
2004, vol. 74, no. 1, p. 139.
0
.89 (chloroform methanol, 6:1). UV spectrum
2. Moskvin, A.V., Platonov, V.G., Il’enko, V.I., and
Ivin, B.A., Abstracts of Papers, Simpozium Novye
(
MeOH), , nm ( ): 325 (3685), 290 (1958).
H NMR spectrum (CDCl ), , ppm: 2.06 s (3H,
max
min
1
podkhody k tselenapravlennomu konstruirovaniyu
3
3
4
H CCO), 3.76 m (2H, C H ), 4.02 m (2H, C H ),
protivovirusnyh preparatov (Symp. New Appro-
aches to Design of Antiviral Preparations ), St. Pe-
tersburg, 1994, p. 6.
3
2
2
1
5
.40 m (2H, C H ), 7.80 8.12 m (5H, C H ), 8.56 s
2 6 5
5
3
(1H, C =CH), 9.6 s (1H, N H). Found N, %: 8.39.
C H N O . Calculated N, %: 8.43.
1
6
16
2
6
3. Kul’pina, G.V., Cand. Sci. (Chem.) Dissertation,
Leningrad, 1990.
5
-[Aryl(hetaryl)methylene]-1-[(2-hydroxyeth-
4
. Levine, H., Brody, R., and Westheinler, F., J. Bio-
chem., 1980, vol. 19, no. 22, p. 4993.
oxy)methyl]barbituric acids VIa VIm (Tables 1
and 2). a. Riboside V, 0.01 mol, was dissolved in
water, and 0.01 mol of corresponding aldehyde was
added. The mixture was heated for 2 3 h at 60 70 C
and left to stand at 18 25 C for 12 15 h. The pre-
cipitate was filtered off, washed with water, and dried
in air to obtain acids VIb, VIe, or VIh in 80 92%
yields.
5. De Clercq, E., Clin. Microbiol. Rev., 1997, vol. 10,
no. 4, p. 674.
6. Kraevsky, A.A. and Watanabe, K.A., Bioinform. M.,
1993.
7
. Moskvin, A.V., Ksenofontova, G.V., Studentsov, E.P.,
and Ivin, B.A., Zh. Obshch. Khim., 1994, vol. 64,
no. 3, p. 492.
b. A solution of 0.01 mol of riboside V in 20 ml
of ethanol, containing 2 ml of acetic acid or without it,
was heated to 80 C, and 0.01 mol of corresponding
aldehyde was added. The mixture was left heated at
that temperature for 1.5 2 h and left to stand at 18
8. Moskvin, A.V., Ksenofontova, G.V., Studentsov, E.P.,
and Ivin, B.A., Zh. Obshch. Khim., 1994, vol. 64,
no. 3, p. 485.
9
. Bojarski, J.T., Mokrocz, J.L., and Barton, H.J., Adv.
Heterocycl. Chem., 1987, vol. 38, p. 229.
2
5 C for 10 15 h. The precipitate was filtered off and
washed with water and a little ethanol to obtain
compounds VIa VIm in 80 99% yields. The pro-
ducts all are colored and chromatographically pure.
1
0. Zoorob, H.H., Abou-El Zahab, M.M., Abdel
Mogib, M., and Ismail, M.A., Tetrahedron, 1996,
-
vol. 52, no. 30, p. 10147.
1
1
1. Figueroa-Villar, J.D. and Cruz, E.R., Tetrahedron,
ACKNOWLEDGMENTS
1
993, vol. 49, no. 14, p. 2855.
2. Ahluwalia, V.K., Sharma, M.K., Aggarwal, R.,
Chauchan, A., and Sharma, R., Indian J. Chem., Sect.
B, 1991, vol. 30, no. 6, p. 598.
The work was financially supported by the Prog-
ram for Support of Basic Research in Natural and
Exact Science of the Ministry of Education of the
Russian Federation (project no. E02-5.0-384,
13. King, F.E., King, T.J., and Thompson, G.B., J. Chem.
Soc., 1948, no. 4, p. 552.
2
003 2004).
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